The destructive lung disorders are diseases in which there is desolution and loss of alveolar structures. The primary mechanism responsible for this is an imbalance of proteases and antiproteases toward proteases, particularly neutrophil elastase. Studies of cigarette smokers have demonstrated that they have neutrophils in their lungs, and the major antielastase of the lower respiratory tract, alpha-1 antitrypsin, is functionally impotent. The alveolar macrophages play a major role in the pathogenesis of cigarette smoking induced emphysema by virtue of their ability to mediate lung injury and recruit neutrophils. Molecular biologic approaches have been used to understand the structure and expression of the alpha-1 antitrypsin gene in order to give insights as to the control of the macromolecule directly responsible for protection of the alveolar structures against elastase.